We form coronas of serum proteins on gold nanorods (NRs) coated with cetyltrimethylammonium bromide (CTAB). These coronas can be exploited for their ability to hold small molecular therapeutics at a capacity much higher (~5-10×) than what covalent conjugation strategies can achieve. Coronas are loaded with DNA oligonucleotides and Doxorubicin, showing that they can hold species of either negative or positive charge. Payload capacity varies with assembly strategy, ionic strength, and loading concentration. Payload release can be achieved by increasing the temperature or by ultrafast laser excitation of the NRs at their longitudinal surface plasmon resonance. DNA leakage from the corona is minimal within the first 3 days of preparation, although Dox leakage was more significant. The coronas also stabilize the NRs in buffer and biological media. This study demonstrates the biological utility of the protein corona around nanomaterials, contrasting the common view of the corona as an undesirable biological response.

Our study shows a facile two-step method which does not require the use of core templates to load a hydrophobic photosensitizer drug chlorin e6 (Ce6) within polydopamine (PDA) nanoparticles (NPs) while maintaining the intrinsic surface properties of PDA NPs. This structure is significantly different from hollow nanocapsules which are less stiff as they do not possess a core. To our knowledge, there exist no similar studies in the literature on drug loading within the polymer matrix of PDA NPs. We characterized the drug loading and release behavior of the photosensitizer Ce6 and demonstrated the therapeutic efficacy of the combined photodynamic (PDT) and photothermal therapy (PTT) from Ce6 and PDA, respectively, under a single wavelength of 665 nm irradiation on bladder cancer cells. We obtained a saturated loading amount of 14.2 ± 0.85 μM Ce6 in 1 nM PDA NPs by incubating 1 mg/mL dopamine solution with 140 μM of Ce6 for 20 h. The PDA NPs maintained colloidal stability in biological media, whereas the pi-pi (π-π) interaction between PDA and Ce6 enabled a release profile of the photosensitizer until day 5. Interestingly, loading of Ce6 in the polymer matrix of PDA NPs significantly enhanced the cell uptake because of endocytosis. An increased cell kill was observed with the combined PDT + PTT from 1 nM PDA-Ce6 compared to that with PTT alone with 1 nM PDA and PDT alone with 15 μM equivalent concentration of free Ce6. PDA-Ce6 NPs could be a promising PDT/PTT therapeutic agent for cancer therapy.

We manipulate the passive release rates of DNA payloads on protein coronas formed around nanoparticles (NPs) by varying the corona composition. The coronas are prepared using a mixture of hard and soft corona proteins. We form coronas around gold nanorods (NRs), nanobones (NBs), and carbon nanotubes (CNTs) from human serum (HS) and find that tuning the amount of human serum albumin (HSA) in the NR-coronas (NR-HS-DNA) changes the payload release profile. The effect of buffer strength, HS concentration, and concentration of the cetyltrimethylammonium bromide (CTAB) passivating the NP surfaces on passive release is explored. We find that corona properties play an important role in passive release, and concentrations of CTAB, HS, and phosphate buffer used in corona formation can tune payload release profiles. These advances in understanding protein corona properties bring us closer toward developing a set of basic design rules that enable their manipulation and optimization for particular biological applications.

We load Ce6 onto NRs using its protein corona, deliver them to cells before performing laser irradiation for simultaneous PTT and PDT with greatly enhanced therapeutic efficacy.